Inclusion Criteria:

1. Histologically proven colorectal adenocarcinoma

2. Intended treatment with mFOLFOX6 after one prior palliative chemotherapy for
metastatic CRC

3. Age > 18 years

4. Metastatic disease not suitable for curative-intent surgery

5. Measurable (> 1 cm) and evaluable disease (according to RECIST 1.1 criteria)

6. Prior bevacizumab, cetuximab or panitumumab are allowed.

7. Previous adjuvant oxaliplatin-containing therapy is allowed, if the end of adjuvant
chemotherapy is >12 months prior to inclusion into the trial

8. ECOG performance status 0 or 1 (see appendix 10.4)

9. Adequate hepatic function

10. Adequate Renal function

11. Adequate bone marrow function

12. Other lab parameters: proteinuria < CTCAE grade 2, Prothrombin time and/or partial
thromboplastin time < 50 % deviation from normal limits

13. Life expectancy at least 3 months

14. Signed and dated written informed consent prior to admission to the study in
accordance with ICH-GCP guidelines and to the local legislation

Exclusion Criteria:

1. Known hypersensitivity to the trial drugs or their excipients.

2. Treatment with any investigational drug within 28 days of trial onset.

3. Prior treatment with more than one line of palliative standard chemotherapy for
colorectal cancer, prior treatment with a tyrosine kinase inhibitor, prior palliative
treatment with an oxaliplatin-containing regime.

4. History of other malignancies in the last 5 years, in particular those which could
affect compliance with the protocol or interpretation of results. Patients with
adequately treated basal or squamous cell skin cancer are generally eligible.

5. Serious concomitant disease, especially those that would limit compliance with trial
requirements or which are considered relevant for the evaluation of the efficacy or
safety of the trial drug, such as neurologic, psychiatric, infectious disease or
active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may
increase the risk associated with trial participation or trial drug administration,
and in the judgment of the investigator would make the patient inappropriate for
entry into the trial.

6. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or
planned surgical procedures during the trial period. Portimplantation prior to
therapy is allowed.

7. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina,
history of infarction within past 9 months, congestive heart failure > NYHA II) (see
appendix 10.3).

8. History of severe haemorrhagic or thrombotic events in the past 12 months (excluding
central venous catheter thrombosis and peripheral deep vein thrombosis). Known
inherited predisposition to bleeds or to thrombosis.

9. Patient with brain metastases that are symptomatic and/or require therapy.

10. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed
for maintenance of an indwelling intravenous device) or antiplatelet therapy (except
for chronic low-dose therapy with acetylsalicylic acid ≤ 325mg per day)

11. History of major thrombotic or clinically relevant major bleeding event in the past 6
months

12. Current peripheral neuropathy ≥ CTCAE grade 2 except due to trauma

13. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial,
antifungal) therapy

14. Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug

15. Active alcohol or drug abuse.

16. Women and men who are sexually active and unwilling to use a medically acceptable
method of contraception

17. Pregnancy or breast-feeding

18. Leptomeningeal disease

19. Radiographic evidence of cavitary or necrotic tumours

20. Centrally located tumours with radiographic evidence (CT or MRI) of local invasion of
major blood vessels

21. Severe chemotherapy-associated toxicity during or after adjuvant or palliative
first-line chemotherapy like 5-FU-associated cardiac toxicity (coronary spasm) or
persistent oxaliplatin-associated peripheral neuropathy (≥ CTCAE grade 2) with
paresthesia associated with pain or functional impairment (after adjuvant
oxaliplatin-containing chemotherapy).