Chemotherapies Associated With Targeted Therapies on the Resection Rate of Hepatic Metastases

Inclusion Criteria:

* Histologically proven colorectal adenocarcinoma,
* Primary tumor of the colon or rectum, resectable or resected at least 3 weeks before randomization or 4 weeks before the beginning of the study treatment,
* Metastatic disease with synchronous or metachronous (\> 3 months after diagnosis of the primary tumor) hepatic metastasis,
* Non-resectable (with respect to curative intent) hepatic metastasis at presentation. This criterion must be validated by both a surgeon and a radiologist during the RCP (Multidisciplinary cancer case presentation committee) patient's evaluation meeting (either technically non-resectable metastases (absolute contraindication): i.e. impossibility to resect all metastases in a single operation while preserving at least 30% of healthy liver tissues and/or impossibility to preserve the portal vein and hepatic artery homolateral to the liver or a portal pedicle, or due to oncological non-resectability (relative contraindication): presence of \> 5 nodules and bilateral invasion),
* Hepatic metastases, without spread to other sites except in case of ≤ 3 resectable pulmonary metastases of diameter \< 2 cm, detected by thoracic scanner,
* K-Ras status determined before randomization,
* Measurable disease according to the RECIST V1.1 criteria,
* No prior treatment of the hepatic metastases,
* Previous 5FU +/- oxaliplatin-based adjuvant chemotherapy administered after colorectal tumor resection is authorized if complete more than 1 year before,
* Age ≥ 18 \& ≤ 75 years
* Performance status : ECOG 0 or 1,
* Life expectancy ≥ 3 months,
* Hemoglobin ≥ 9 g/dl,
* Polynuclear neutrophiles ≥ 1500/mm3,
* Platelets ≥ 100 000 mm3,
* Creatinemia ≤ 135 µmol/l (1,35 mg/dl)
* Total bilirubin ≤ 1.25 times the Upper Limit of Normal (ULN).
* Hepatic enzymes ASAT and ALAT \< 5 x ULN,
* Negative pregnancy test for women of child-bearing age,
* Information given to the patient and signed informed consent,
* Public Health insurance coverage.

Exclusion Criteria:

* Non metastatic and/or non measurable disease according to the RECIST v1.1 criteria.
* Non-resectable primary tumor (e.g.: T4 tumors) or incomplete resection R2.
* History of intestinal inflammatory disease.
* Specific contraindication to any of the study treatments.
* Patient who have previously received anti-EGFr (e.g., cetuximab) or anti-VEGF monoclonal antibody treatment (e.g., bevacizumab) or treatment with irinotecan.
* History of cancer considered as not cured.
* Stroke/CVA or pulmonary embolism within 6 months before inclusion.
* Significant concomitant disease such as: coagulopathy, respiratory or cardiac congestive insufficiency, non-medically controlled/unstable angina pectoris, myocardial infarction within 6 months prior to study entry, arterial hypertension and uncontrolled arrhythmia, severe infections.
* Clinical neuropathy, grade ≥1.
* Patient already included in another therapeutic trial using an experimental molecule.
* Pregnant women or women who might become pregnant during the study or lactating women.
* Men or women who can procreate and who do not abide with the use of a contraceptive means.
* Persons kept in detention or incapable of giving consent
* Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic social or psychological reasons.