Bevacizumab (Bev), a monoclonal antibody against vascular endothelial growth factor, when combined with standard first-line chemotherapy, shows impressive clinical benefit in advanced non-squamous non-small cell lung cancer (ns-NSCLC). Our study aims to investigate whether the addition of Bev to pemetrexed improves progression-free survival (PFS) in advanced ns-NSCLC patients after the failure of at least one prior chemotherapy regimens. Patients with locally advanced, recurrent, or metastatic ns-NSCLC, after failure of platinum-based therapy, with a performance status 0 to 2, were eligible. Patients received 500 mg/m(2) of pemetrexed intravenously (IV) day 1 with vitamin B12, folic acid, and dexamethasone and Bev 7.5 mg/kg IV day 1 of a 21-day cycle until unacceptable toxicity, disease progression or the patient requested therapy discontinuation. The primary end point was PFS. Between December 2011 and October 2013, 33 patients were enrolled, with median age of 55 years and 36.4% men. Twenty-three patients (69.7%) had received two or more prior regimens, and 28 patients (84.8%) had received chemotherapy containing pemetrexed. The median number of the protocol regimens was 4. Median PFS was 4.37 months (95% CI 2.64-6.09 months). Median overall survival (OS) was 15.83 months (95% CI 10.52-21.15 months). Overall response rates were 6.45%. Disease control rate was 54.84%. No new safety signals were detected. No patient experienced drug-related deaths. The combination of Bev and pemetrexed every 21 days is effective in ns-NSCLC patients who failed of prior therapies with improved PFS. Toxicities are similar with historical data of these two agents and are tolerable. Our results may provide more a regimen containing Bev and pemetrexed for Chinese clinical practice in previously treated ns-NSCLC.