OBJECTIVES: Stage IV CRC patients have varying survival results from multiple lines of treatment. The objective of this study was to evaluate in a real world context, the impact of adding a third line of chemotherapy to a stage IV CRC population. METHODS: The Georgia Cancer Specialist database (2005-2011) was used. Patients with stage IV colon or rectal cancer and treated with chemotherapy were followed from initial CRC diagnosis until death, study end or lost to follow-up. Patients were stratified into lines and type of protocol for treatments. Kaplan-Meier curves were used to compare the overall survival results between lines of therapy.    RESULTS: There were 335 patients with confirmed stage IV CRC of which 35% received one protocol, 27% two protocols, and 38% received three or more protocols. The most common first line agents consisted of FOLFOX with or without bevacizumab or FOLFIRI with or without bevacizumab. Some single agent 5FU or 5FU with bevacizumab was observed in first line. The most common second agents were the FOLFOX or FOLFIRI not given in first line. However single agent capecitabine, cetuximab and bevacizumab were observed. In third line similar single agents but more panitumumab and capecitabine combinations were observed. Of those treated with second line (45) and three or more lines (75). The median survival was no different between the patients that received second line and those that went on to a third line (Log-Rank P=0.1249) CONCLUSIONS: The addition of adding a third line to a stage IV population that already received a second line failed show an association to increase survival. The benefit of adding a third line may benefit some patients and the particular combination of therapy needs to be explored in future studies.