OBJECTIVES: Optimal therapy and associated survival benefit for patients with stages IIIB/C and IV colorectal cancer (CRC) have not been well established. The aim of this study was to examine treatment patterns and survival among CRC patients who received 2nd and 3rd line regimens. METHODS: A retrospective analysis was performed using the Georgia Cancer Specialist Database.  Patients 18 years and older diagnosed with stage IIIB/C or IV CRC between January, 2006 and November, 2012 were followed from initial CRC diagnosis until death, study end or loss to follow-up. Regimen concordance with National Comprehensive Cancer Network (NCCN) treatment guidelines was assessed.  Survival was compared between patients who initiate second- versus third-line regimens using Cox proportional hazards models. RESULTS: 1081 patients were identified, 542 with stage IIIB/C and 539 with stage IV CRC. The most common first line regimens were FOLFOX (32% of patients) and FOLFOX with bevacizumab (18% of patients).  In discordance with the NCCN guidelines, 16% of patients received monotherapy as first line.  544 patients (50%) received second line therapy; the most common regimen was bevacizumab plus IFL (14% of patients who received second line therapy).  Approximately 25% of patients (n=269) received third line therapy.  The most common therapies were irinotecan/cetuximab, bevacizumab monotherapy, and capecitabine monotherapy (10% of 3rd line patients, respectively).  73% of 3rd line patients had ECOG performance scores of zero or one.  Survival was significantly worse in stage IV patients who received 3rd line therapy versus those who stopped at 2nd line (p=0.004). CONCLUSIONS: Most patients received treatment in accordance with NCCN guidelines; however, a substantial proportion received monotherapy as first line.  There was no survival benefit observed in stage IV patients who began a third line therapy. The subpopulation of patients who may benefit from 3rd line therapy should be explored in future studies.