Targeted monoclonal antibodies bevacizumab, cetuximab and panitumumab are reimbursed in the Czech Republic in combination with chemotherapy or alone in metastatic colorectal cancer (mCRC). However, the high cost is a potentially limiting factor. The real-world costs and effectiveness of first line bevacizumab followed by cetuximab or panitumumab (EGFRi) were retrospectively assessed from the perspective of healthcare payer. Total 71 WT KRAS patients (56% men; median age 60.5 years) were evaluated between April 2007 and May 2017. During our follow-up period (30 months on average) 55% patients died. The mean cost to PD was EUR 32,107 and EUR 24,510 in bevacizumab and EGFRi treatment respectively with median PFS 9.7 and 5.0 months. The median overall survival was 27.2 months and the mean cost from sequential therapy initiation to death was EUR 63,682. The targeted therapy made up 77%, 86% and 76% of the costs in the first line, second line and from the initiation of sequential therapy to death respectively.