Efficacy of Chemotherapy, Associated to Either Cetuximab or Bevacizumab, in KRAS Wild-type Metastatic Colorectal Cancer Patients With Progressive Disease After Receiving First-line Treatment With Bevacizumab

Inclusion Criteria:

* Histologically or cytologically proven adenocarcinoma of the colon expressing non-mutated (wild-type) KRAS.
* Progressive metastatic disease after first-line treatment with chemotherapy alone: based on 5-FU (iv or per os) with irinotecan or oxaliplatin associated to bevacizumab.
* Prior adjuvant chemotherapy (of the primary tumor) with fluoropyrimidine and oxaliplatin is allowed if the time interval between the end of this chemotherapy and the beginning of the first-line metastatic treatment is ≥ 6 months.
* Measurable disease (at least one measurable metastatic lesion) according to the RECIST V1.1 criteria (the lesion should not be located in a previous field of radiation).
* Previous radiotherapy is authorized if discontinued ≥ 15 days prior to randomization and if the measurable metastatic lesions are outside the radiation area.
* Sites of disease evaluated within 28 days prior to randomization with thoracic-abdominal-pelvic CT scan (or abdominal-pelvic MRI plus Chest Xray)
* Age ≥18 years
* Patient with ECOG 0 or 1
* Life Expectancy ≥ 3 months
* Hematologic function (polynuclear neutrophiles ≥ 1.5.109/L ; platelets ≥ 100.109/L ; hemoglobin ≥ 9 g/dL
* Hepatic transaminases ≤ 2.5 times upper limit of normal (ULN) (≤ 5 ULN in case of hepatic metastases), alkaline phosphatases ≤ 2.5 ULN (≤ 5 ULN in case of hepatic metastases), total bilirubinemia ≤ 1.5 ULN
* Renal function (creatinemia ≤1.5 ULN; creatine clearance ≥ 50 mL/mn (Cockcroft and Gault) ; urine test strip \< 2+. If proteinuria is ≥ +2 at inclusion, the serum urea test must be redone and show proteinuria ≤ 1 g/L within 24 h)
* Completion of the EORTC QLQ-C30 quality of life form
* Negative pregnancy test for women of child-bearing age
* Information given to the patient and signed informed consent
* Public Health insurance coverage

Exclusion Criteria:

* Known meningeal or brain metastases
* Pre-treatment with anti-EGFR
* Specific contraindication or known hypersensitivity to one treatment product
* Patient with known allergy or hypersensitivity to monoclonal antibodies (bevacizumab, cetuximab
* Clinically significant affection of the coronaries or myocardial infarction within 6 months prior to inclusion.
* Peripheral neuropathy of grade \> 1 (CTCAE scale version 4.0).
* Known depletion of the dihydropyrimidine dehydrogenase (DPD).
* Acute intestinal obstruction or sub-obstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colic prosthesis.
* Uncontrolled Arterial hypertension (systolic pressure \> 150 mmHg and/or diastolic pressure \> 100 mmHg with and without antihypertensive medication. Patients with high hypertension are eligible if antihypertensive medication lowers their arterial pressure to the level of acceptability specified by the inclusion criteria.
* History of hypertensive crisis or hypertensive encephalopathy
* Other concomitant malignancy or history cancer (except carcinoma in situ of the cervix, or non melanoma skin cancer, with curative intent treatment, when considered in complete remission for at least 5 years before randomization.
* Any treatment including an experimental drug, or participation in another clinical trial within 28 days preceding inclusion.
* Persons deprived of liberty or under guardianship.
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.