Critères d'inclusion : - Age between 18 and 75 years
- ECOG PS between 0 and 1
- Histologically confirmed adenocarcinoma of the colon or rectum
- Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent
- K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf (codon 600) wild-type tumor status according to plasma analysis of circulating cell free DNA by Intplex technology
- Measurable disease according to RECIST version 1.1
- Adequate hematologic, hepatic and renal functions:
-> Absolute neutrophil count (ANC) ≥2 x 109/L
-> Haemoglobin ≥9 g/dL
-> Platelets (PTL) ≥100 x 109/L
-> AST/ALT ≤5 x ULN
-> Alkaline phosphatase ≤2.5 x ULN
-> Bilirubin ≤1.5 x ULN
-> Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)
- Life expectancy of at least 3 months
- Adequate contraception if applicable
- Patient affiliated to a social security regimen
- Patient information and signed written consent form
Critères de non-inclusion : - History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
- Adjuvant treatment with oxaliplatin
- Previous treatment for metastatic disease
- Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test
- Brain metastases
- Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study
- Patient with history of pulmonary fibrosis or interstitial pneumonitis
- Previous organ transplantation, HIV or other immunodeficiency syndromes
- Concomitant medications/comorbidities that may prevent the patient from receiving study treatment as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension…)
- Persistent peripheral neuropathy >grade1 (NCI CT v4.03)
- Ionic disorders as:
-> Kalemia ≤1 x ULN
-> Magnesemia <0.5mmol/L
-> Calcemia <2mmol/L
- Patient with known dihydropyrimidine dehydrogenase deficiency
- QT/QTc>450msec for men and >470msec for women
- Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)
- Concomitant intake of St. John's wort
- Other concomitant cancer
- Patient participating another clinical trial
- Pregnant woman or lactating woman
- Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule
- Legal incapacity or limited legal capacity