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)