OBJECTIVES:  Colorectal cancer (CRC) is a major burden of disease and a key contributor to healthcare costs internationally. Available treatment options, especially for the metastatic phase of the disease, are numerous and are accompanied by varying degrees of efficacy and costs. Bearing in mind the quest for efficiency, the purpose of this analysis was to estimate the budget impact of the most frequently used treatment options for CRC in Greece. METHODS: The analysis is based on a budget impact model that estimates the costs of alternative treatment approaches in patients with metastatic CRC, depending on the presence of RAS mutations. Data on the clinical effectiveness of the interventions under review were obtained from published literature, whereas the most frequently used treatment algorithms (treatment strategies) in Greece were developed by an expert panel of 11 oncologists. The analysis follows a third party payer perspective and costs are in year 2015 Euros. RESULTS:  For patients without RAS mutations, the average cost/patient for the strategy of FOLFOX/CapeOX plus bevacizumab (1st line), FOLFIRI plus anti-EGFR (2nd line) and chemotherapy alone (3rd line) was estimated at €35,186, while for a strategy of FOLFOX/CapeOX plus anti-EGFR (1st line), FOLFIRI plus aflibercept (2nd line) and chemotherapy alone (3rd line) the average cost per patient was €49,225. For patients with RAS mutations, the corresponding cost per treatment strategy was €29,542 (FOLFOX/CapeOX plus bevacizumab -FOLFIRI plus aflibercept – chemotherapy alone) and €31,161 (FOLFOX/CapeOX - FOLFIRI plus aflibercept – chemotherapy alone). CONCLUSIONS:  Based on the available epidemiological data for Greece, there are currently 2,054 metastatic CRC patients under treatment. According to the results of the present study (and not withstanding its limitations), bevacizumab-based strategies could lead to an average reduction of €8,312/patient under treatment or at an excess 524 patients that could receive treatment, under the current pharmaceutical expenditure levels for CRC.