To compare the activity and tolerance of the consecutive administration of four active chemotherapeutic agents in combination with bevacizumab to a bevacizumab- and platinum-based chemotherapy doublet as front-line treatment in patients with non-squamous NSCLC.Patients with advanced/metastatic NSCLC, performance status of 0–2 and normal organ function were randomized to receive either 3 cycles every 3 weeks of cisplatin 80mg/m2 (day 1), oral vinorelbine 60mg/m2 (days 1 and 8) and bevacizumab 15mg/kg (day 1) every 3 weeks (VCB regimen) followed by 3 cycles of docetaxel (75mg/m2, day 1), gemcitabine (1100mg/m2, days 1 and 8) and bevacizumab 15mg/kg (day 1) (DGB regimen) (arm A) or 6 cycles of cisplatin 80mg/m2, docetaxel 75mg/m2 and bevacizumab 15mg/kg on day 1 (DCB regimen; arm B) every 3 weeks.Thirty-eight and 39 patients were enrolled in arm A and B, respectively. The study did not meet its primary endpoint since, the ORR was 39.5% (95% CI: 23.9–55.0%; 1CR and 14 PR) and 46.2% (95% CI: 30.5–61.8%; 2 CR and 16 PR) in arm A and B, respectively (p=0.554). There was no significant difference in terms of response duration (7.4 versus 4.7 months in arm A and B, respectively; p=0.697), progression-free survival (5.8 versus 5.5 months, respectively; p=0.540) and overall survival (16.9 versus 10.9 months; p=0.390). No difference was recorded between the two arms regarding the toxicity profile. There were two drug-related deaths in arm B.Sequential therapy of VCB followed by DGB is a feasible and well-tolerated regimen but failed to show any superiority over the standard DCB regimen.