Inclusion Criteria:

Signed written informed consent

• Inpatient or outpatient subjects, 18 years of age
• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
• Metastatic disease (M1)
• Life expectancy of at least 12 weeks
• Presence of at least 1 measurable index lesion (not lie in an irradiated area) by CT scan or MRI
• ECOG performance status of 0 or 1 at study entry
• Effective contraception for both male and female subjects if the risk of conception exists
• White blood cell count ≥ 3,000/mm3 with neutrophils ≥ 1,500/mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 5.6 mmol/L (9 g/dL)
• Total bilirubin ≤ 1.5 x upper reference range
• AST ≤ 2.5x upper reference range, or ≤ 5x upper reference range in case of liver metastasis
• Serum creatinine ≤ 1.5x upper reference range
• Recovery from relevant toxicity to previous treatment before study entry
• KRAS wild-type status of tumor tissue - Tissue should also be available for other biomarker determinations

Exclusion Criteria:

• Previous chemotherapy for colorectal cancer except adjuvant treatment if terminated > 6 months before the start of treatment in this study
• Radiotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
• Concurrent chronic systemic immune therapy, targeted therapy, anti-VEGF therapy, or EGFR-pathway targeting therapy not indicated in this study protocol
• Concurrent hormone therapy not indicated in this study protocol except for physiologic replacement or contraception
• Known hypersensitivity reaction to any of the components of study treatments
• Pregnancy (absence to be confirmed by ß-hCG test) or lactation period
• Brain metastasis and/or leptomeningeal disease (known or suspected)
• Clinically relevant coronary artery disease, history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
• Peripheral neuropathy > grade 1
• Previous malignancy other than colorectal cancer in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
• Known alcohol or drug abuse
• Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent
• Participation in another clinical study within the past 30 days
• Significant disease which, in the investigator's opinion, would exclude the patient from the study
• Legal incapacity or limited legal capacity
• KRAS mutated status of tumor tissue