The primary objective of this trial is to explore the overall objective best response rate and the rate of non-progression at 16 weeks of sequential, alternating weekly administration of BIBF 1120 and BIBW 2992 in patients with metastatic CRC based on the RECIST criteria.

Inclusion Criteria:

1. Age over 18 years.
2. Signed informed consent.
3. Histologically proven colorectal adenocarcinoma
4. History or presence of metastatic colorectal cancer (stage IV)
5. Measurable (>1 cm) or evaluable tumour deposit (according to RECIST criteria)
6. Documented progression or unacceptable toxicity on the last therapy
7. Progression on oxaliplatin-based chemotherapy or unacceptable residual neurotoxicity on oxaliplatin
8. Progression on irinotecan-based chemotherapy or unacceptable toxicity on irinotecan
9. If patients have been previously exposed to Cetuximab or other EGFR inhibitor, they must have shown progression or unacceptable toxicity
10. If patients have been previously exposed to Bevacizumab or other VEGF inhibitor, they must have shown progression or unacceptable toxicity
11. Life expectancy of at least 12 weeks.
12. WHO (ECOG) performance status <= 2, <= 1 if age > 75 years.
13. Adequate hepatic function
14. Adequate renal function

Exclusion Criteria:

1. Prior treatment with small molecule EGFR, HER2 or VEGFR tyrosine kinase inhibitors
2. Treatment with standard chemotherapy or cetuximab within the last 14 days
3. Treatment with bevacizumab within the last 28 days
4. History of other malignancies in the last 5 years, which could affect compliance with the protocol or interpretation of results. Patients with adequately treated basal or squamous cell skin cancer are generally eligible.
5. Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality
6. Significant cardiovascular diseases
7. History of haemorrhagic or thrombotic event in the past 12 months. Known inherited predisposition to bleeds or to thrombosis.
8. Patient with history or clinical or radiological evidence of CNS disease or brain metastases.
9. Pregnancy or breast-feeding