Inclusion Criteria:

1. Signed and dated informed consent, and willing and able to comply with protocol
requirements,

2. Histologically proven adenocarcinoma of the colon and/or rectum,

3. Metastatic disease confirmed,

4. No prior therapy for metastatic disease (in case of previous adjuvant therapy,
interval from end of chemotherapy to relapse must be >6 months for fluoropyrimidine
alone or >12 months for oxaliplatin-based, bevacizumab-based, cetuximab-based
therapy,

5. Duly documented inoperable metastatic disease, ie not suitable for complete
carcinological surgical resection,

6. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic
Resonance Imaging) according to RECIST v1.1,

7. Age ≥18 years,

8. ECOG Performance status (PS) 0-2,

9. Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; haemoglobin
≥9g/dL,

10. Adequate renal function: serum creatinine level <150µM,

11. Adequate liver function: serum bilirubin ≤3 x upper normal limit (ULN), alkaline
phosphatase <5xULN,

12. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour,

13. Baseline evaluations: clinical and blood evaluations performed no more than 2 weeks
(14 days) prior to confirmation of eligibility, tumor assessment (chest X ray,
CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days)
prior to confirmation of eligibility,

14. For female patients of childbearing potential, negative serum or urine pregnancy test
within 1 week (7 days) prior of starting study treatment,

15. Female patients of childbearing potential must commit to using reliable and effective
methods of contraception during the trial and until at least six months after the end
of study treatment. Females are neither pregnant nor in breastfeeding. Male patients
with a partner of childbearing potential must agree to use effective contraception in
addition to the contraceptive method used by their partner during the trial and until
at least six months after the end of study treatment.

16. Registration in a national health care system (CMU included for France).

Exclusion Criteria:

1. History or evidence upon physical examination of CNS metastasis unless adequately
treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard
medical therapy),

2. Exclusive bone metastasis,

3. Uncontrolled hypercalcemia,

4. Pre-existing permanent neuropathy (NCI grade ≥2),

5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or
diastolic blood pressure >100 mmHg despite optimal medical therapy), or history of
hypertensive crisis, or hypertensive encephalopathy,

6. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted
therapy, immunotherapy/ radio-immunotherapy),

7. Treatment with any other investigational medicinal product within 28 days prior to
study entry,

8. Other serious and uncontrolled non-malignant disease,

9. Other concomitant or previous malignancy, except: i/ adequately treated in-situ
carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin,
iii/ cancer in complete remission for >5 years,

10. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic
injury within the last 28 days

11. Patients with known allergy to any excipient to study drugs,

12. History of myocardial infarction and/or stroke within 6 months prior to study entry,

13. Bowel obstruction.