A prospective, open, multicenter, randomized III trial with two arms:

• Arm A: Primary tumor resection , followed by chemotherapy
• Arm B: Chemotherapy alone. Compare overall 2-year survival rates in patients treated for resectable rectal adenocarcinoma with unresectable metastasis, treated either with the primary tumor resection with chemotherapy +/- target therapy, or with chemotherapy (+/- target therapy) alone.

Inclusion Criteria:

• Non-complicated primary tumor (i.e. tumor without obstruction, bleeding, abscess or perforation requiring emergency surgery and/or contra-indicating first-line chemotherapy)
• Unresectable synchronous metastases
• ECOG performance status 0-1
• Rectal adenocarcinoma (<15 cm from the anal verge) with few or no symptoms and unresectable metastasis (assessed by the investigator) unsuitable for curative treatment
• No known unresectable primary tumor (with clear margin >1mm) on CT-scan and MRI
• No disease progression under chemotherapy (for at least 4 cycles);
• Assessment of KRAS status before randomization (wild type or mutated);
• Life expectancy without cancer >2 years
• White blood cell count ≥ 3 x 109/L, with neutrophils ≥ 1,5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin°≥ 9 g/dL (5,6 mmol/l)
• Total bilirubin ≤ 1.5 x ULN (upper limit of normal), ASAT and ALAT ≤ 2.5 x ULN, alkaline phosphatase°≤°1.5°x ULN, serum creatinine ≤ 1.5 x ULN;
• Age ≥ 18 years ≤ 75 years
• Patients with childbearing potential should use effective contraception during the study and up 6 months after the end of chemotherapy
• Covered by a Health System where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;
• Signed written informed consent obtained prior to any study-specific screening procedures

Exclusion Criteria:

• Rectal tumor operated before inclusion
• Symptoms related to the rectal tumor requiring first intention rectal surgery (appreciated by investigator)
• Contra-indication for surgery
• Resectable metastases
• Complicated (obstruction, bleeding, abscess, perforation) primary tumor requiring emergency surgery and/or contra-indicating first line-chemotherapy
• Non-resectable primary tumor (with wild margin)
• Age > 75 years < 18 years
• ECOG performance status > 2
• Under nutrition (albumin < 30 g/l)
• Peritoneal carcinomatosis
• Disease progression under chemotherapy (RECIST 1.1 criteria)
• Known hypersensitivity reaction or specific contraindications to any of the components of study treatments
• Clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
• Pregnancy (absence to be confirmed by ß-hCG test) or breast-feeding;
• Previous malignancy in the last 5 years
• Medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent; in the investigator's opinion
• Any significant disease which, in the investigator's opinion, excludes the patient from the study
• Under an administrative or legal supervision.