<br>        Inclusion Criteria:<br><br>          1. Histologically proven colorectal adenocarcinoma<br><br>          2. Intended treatment with mFOLFOX6 after one prior palliative chemotherapy for<br>             metastatic CRC<br><br>          3. Age > 18 years<br><br>          4. Metastatic disease not suitable for curative-intent surgery<br><br>          5. Measurable (> 1 cm) and evaluable disease (according to RECIST 1.1 criteria)<br><br>          6. Prior bevacizumab, cetuximab or panitumumab are allowed.<br><br>          7. Previous adjuvant oxaliplatin-containing therapy is allowed, if the end of adjuvant<br>             chemotherapy is >12 months prior to inclusion into the trial<br><br>          8. ECOG performance status 0 or 1 (see appendix 10.4)<br><br>          9. Adequate hepatic function<br><br>         10. Adequate Renal function<br><br>         11. Adequate bone marrow function<br><br>         12. Other lab parameters: proteinuria < CTCAE grade 2, Prothrombin time and/or partial<br>             thromboplastin time < 50 % deviation from normal limits<br><br>         13. Life expectancy at least 3 months<br><br>         14. Signed and dated written informed consent prior to admission to the study in<br>             accordance with ICH-GCP guidelines and to the local legislation<br><br>        Exclusion Criteria:<br><br>          1. Known hypersensitivity to the trial drugs or their excipients.<br><br>          2. Treatment with any investigational drug within 28 days of trial onset.<br><br>          3. Prior treatment with more than one line of palliative standard chemotherapy for<br>             colorectal cancer, prior treatment with a tyrosine kinase inhibitor, prior palliative<br>             treatment with an oxaliplatin-containing regime.<br><br>          4. History of other malignancies in the last 5 years, in particular those which could<br>             affect compliance with the protocol or interpretation of results. Patients with<br>             adequately treated basal or squamous cell skin cancer are generally eligible.<br><br>          5. Serious concomitant disease, especially those that would limit compliance with trial<br>             requirements or which are considered relevant for the evaluation of the efficacy or<br>             safety of the trial drug, such as neurologic, psychiatric, infectious disease or<br>             active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may<br>             increase the risk associated with trial participation or trial drug administration,<br>             and in the judgment of the investigator would make the patient inappropriate for entry<br>             into the trial.<br><br>          6. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or<br>             planned surgical procedures during the trial period. Portimplantation prior to therapy<br>             is allowed.<br><br>          7. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina,<br>             history of infarction within past 9 months, congestive heart failure > NYHA II) (see<br>             appendix 10.3).<br><br>          8. History of severe haemorrhagic or thrombotic events in the past 12 months (excluding<br>             central venous catheter thrombosis and peripheral deep vein thrombosis). Known<br>             inherited predisposition to bleeds or to thrombosis.<br><br>          9. Patient with brain metastases that are symptomatic and/or require therapy.<br><br>         10. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed<br>             for maintenance of an indwelling intravenous device) or antiplatelet therapy (except<br>             for chronic low-dose therapy with acetylsalicylic acid = 325mg per day)<br><br>         11. History of major thrombotic or clinically relevant major bleeding event in the past 6<br>             months<br><br>         12. Current peripheral neuropathy = CTCAE grade 2 except due to trauma<br><br>         13. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial,<br>             antifungal) therapy<br><br>         14. Gastrointestinal disorders or abnormalities that would interfere with absorption of<br>             the study drug<br><br>         15. Active alcohol or drug abuse.<br><br>         16. Women and men who are sexually active and unwilling to use a medically acceptable<br>             method of contraception<br><br>         17. Pregnancy or breast-feeding<br><br>         18. Leptomeningeal disease<br><br>         19. Radiographic evidence of cavitary or necrotic tumours<br><br>         20. Centrally located tumours with radiographic evidence (CT or MRI) of local invasion of<br>             major blood vessels<br><br>         21. Severe chemotherapy-associated toxicity during or after adjuvant or palliative<br>             first-line chemotherapy like 5-FU-associated cardiac toxicity (coronary spasm) or<br>             persistent oxaliplatin-associated peripheral neuropathy (= CTCAE grade 2) with<br>             paresthesia associated with pain or functional impairment (after adjuvant<br>             oxaliplatin-containing chemotherapy).<br>