Inclusion Criteria:

• Histologically verified colorectal adenocarcinomas
• Age > 18 years and < 70
• Metastatic colorectal cancer refractory 5-FU, oxaliplatin and irinotecan containing treatment regimes
• KRAS mutation detected by DxS kit in primary tumor or metastatic lesion.
• Measurable disease according to RECIST
• ECOG performance status 0, 1 or 2
• Adequate renal, hepatic and haematological function
• Normal serum cholesterol and triglycerides
• Blood samples and available paraffin embedded tumor material for translational research studies
• Fertile males and females (< 2 years after last period for women) must use effective birth control
• Signed Informed consent

Exclusion Criteria:

• Clinically significant heart disease, active severe infections or other concurrent disease
• Other malignant diseases within 5 years of inclusion in the study, except basal cell squamous cell carcinoma of the skin and cervical carcinoma-in-situ
• Prior radiotherapy within 30 days of treatment start
• Other experimental therapy within 30 days of treatment initiation
• Patients who are breast feeding, childbearing or of childbearing potential without using dual effective contraception
• Clinical or radiological evidence of CNS metastasis

• Completed any major surgery, excision biopsy or significant traumatic lesion ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment

  • Insertion of a vascular access device is not considered major or minor surgery from the viewpoint of protocol eligibility
  • Patients must have fully recovered from the procedure and have a fully healed incision
• Planned radiation therapy against target-lesions
• Patients with significant non-healing wounds or ulcers

• History or evidence of thrombotic or hemorrhagic disorders

  • Significant haemorrhage (> 30 ml/bleeding episode in previous 3 months)
  • Haemoptysis (> 5 ml fresh blood in previous 4 weeks)

• Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met:

  • The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin
  • The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoid Hemorrhage (SAH) within 12 months prior to randomization
• No known or history of HIV seropositivity
• The use of ACE inhibitors is not permitted during the study
• Known allergy to temsirolimus, sirolimus, polysorbate 80 or included agents.
• Agents with strong CYP3A4-inhibitory potential