The main objective of this study is to evaluate the objective response rate at two months (complete disappearance of the disease and partial disappearance of the disease) obtained after administration of combination therapy with cetuximab and irinotecan in the patients with metastatic colorectal cancer.

Secondaries objectives will be assessed progression-free survival, overall survival, toxicity, quality of life.

Inclusion Criteria:

• Signed and dated informed consent
• Histologically confirmed metastatic adenocarcinoma of the colon or rectum
• All Wild Type KRAS (exon 2 [codons 12-13], exon 3 [codons - 61]; exon 4 [codon 146]), NRAS (exon 2 [ codons 12-13] and exon 3 [codon 61) and BRAF (V600E) tumor ( local assessment performed either on primary tumor or metastasis)
• First line chemotherapy regimen with a fluoropyrimidine and Irinotecan (FOLFIRI) + cetuximab with initial partial or complete response and progressive disease (PD) with PD ≤ 6 weeks after the last administration of cetuximab
• Other line(s) of therapy(ies) including the following drugs: second line oxaliplatin based chemotherapy with fluoropyrimidines (5FU or capecitabine) + bevacizumab and eventually regorafenib (possible but not mandatory) and progression or limiting toxicity to the last therapy with a minimum of 4 months between last injection of cetuximab and inclusion in this study
• At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1 (All sites must be evaluated ≤ 28 days prior to the enrolment)
• Age ≥18 years
• World Health Organization (WHO) Performance status (PS) 0-2
• The patient has adequate organ function, defined as :

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 100 x 109/L.Total bilirubin ≤ 1.5 times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times ULN, Serum creatinine level <150μM/l

• For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug
• Men and women are required to use adequate birth control during the study (when applicable) and until 6 months after the end of study treatment
• Registration in a national health care system (CMU included)

Exclusion Criteria:

• Previous chemotherapy other than adjuvant therapy with different combinations than those scheduled in first and second line treatment
• Presence of any KRAS, BRAF or NRAS mutation by allelic discrimination on tumor DNA
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiation of study treatment or a history of ventricular arrhythmia (treated or not)
• History or evidence of central nervous system metastasis (systematic CT-scan or MRI not mandatory if no clinical symptoms)
• Known allergy or hypersensitivity to cetuximab
• Previous or concurrent malignancy except for basal or squamous cell skin cancer, in situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico classification or other solid tumors treated curatively and without evidence of recurrence for at least 5 years prior to the study
• Active or uncontrolled clinically serious infection
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
• Other serious and uncontrolled non-malignant disease
• Pregnancy
• Breast feeding
• Treatment with any other investigational medicinal product within 28 days prior to study entry
• Known Gilbert's syndrome
• Concomitant administration of live, attenuated virus vaccine such as yellow fever vaccine
• Concomitant use with St John's Wort
• Chronic inflammatory bowel disease and/or Bowel obstruction](streamdown:incomplete-link)