2nd-line Treatment of Metastatic Colorectal Cancer

Inclusion Criteria: * Histologically proven colorectal cancer * Resected or asymptomatic primary tumor * Metastatic colorectal cancer not eligible for curative surgery * No major surgery within four weeks of the start of study treatment * At least one target lesion unidimensionally measurable on cross-sectional imaging according to RECIST criteria (v1.1) * Disease progression after failure of irinotecan-based chemotherapy * Bone metastases are allowed if there is at least one other measurable metastatic site * CT scan of the abdomen, chest and pelvis within 3 weeks of the start of study treatment * WHO PS ≤ 2 * Platelet count \>= 100,000 mm3 * Hemoglobin \> 10g/dl * Bilirubin \< 1.5 ULN, AST/ALT \< 5 ULN * Serum creatinine \< 1.5 ULN, creatinine clearance \> 60 ml/min (Cockcroft) * A time period of 4 weeks should be respected between the end of previous treatments and study enrollment * Negative pregnancy test in women of childbearing potential * Male or female using an effective contraceptive method * Absence of known or symptomatic brain metastases * Life expectancy \> 3 months * Informed consent signed prior any study specific procedures Exclusion Criteria: * Prior raltitrexed-based chemotherapy * Prior oxaliplatin-based chemotherapy (except for adjuvant treatment completed for more than 6 months) * Uncontrolled arterial hypertension defined as systolic pressure \> 150 mm Hg or diastolic pressure \> 100 mm Hg * Malignant hypertension or hypertensive encephalopathy * Myocardial infarction, pulmonary embolism, or severe vascular disease within 6 months prior to study entry * Hemorrhagic diathesis or significant pathology of coagulation * Peripheral neuropathy grade\>2 (NCI-CTC v4.0) * Hemoptysis \< 1 month * Venous access device (PAC) or any other minor surgery such as a biopsy within the last 7 days * Symptomatic brain metastases or carcinomatous meningitis * History or presence of other cancer within the past 5 years (except curatively treated nonmelanoma skin cancer and in situ cervical cancer) * Severe bacterial or fungal infection (Grade \> 2 NCI-CTCAE v.4.0) * Known or suspected sensitivity to one of the study drugs * Pregnant or breastfeeding women * Previous enrollment in an investigational drug study within the last 4 weeks * Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up)