Chemotherapy resistance is a major challenge in metastatic colorectal cancer (mCRC), and EGFR inhibitors have been introduced as 3rd line treatment to chemotherapy refractory patients. However, it has recently been established that response to treatment with irinotecan and cetuximab is confined to patients with wtKRAS tumors. Therefore, downstream targets are being proposed as potential inhibitors of the EGFR signalling in tumours with KRAS mutations. mTOR is a central intracellular signalling molecule and a rational approach for potential reversion of chemotherapy resistance in these patients.