Colorectal cancer (CRC) is one of the most frequent malignancies, with more than 1,000,000 new cases annually worldwide and more than 4,000 new cases annually in Bulgaria. Liver metastases (LM) occur in more than 50% of CRC patients, but curative liver resection is possible only in 15% of them, resulting in 5-year survival rates of 30% on average. Improving resectability rates and hopefully patient's prognosis by adding up front active chemotherapy and biological agents in metastatic CRC is a challenging opportunity for both medical and surgical oncologists. This review encompasses clinical trials of modern chemotherapy combinations in metastatic CRC and their application as neoadjuvant therapy before liver surgery. The different surgical methods for improving resectability of LM in patients with CRC are also discussed. In the neoadjuvant setting an emerging concern about chemotherapy-induced liver toxicity gained further attention. The recent data of liver injury following up front systemic chemotherapy are revealed. The impact of anti-angiogenesis agents on liver regeneration and wound healing, which is not yet fully understood, is being discussed, focusing on patient-to-patient individualized decision by multidisciplinary team.