An overview of recent works (1998–2002) coupling Advanced Oxidation Process (AOP) and Biological systems for wastewater treatment confirms the beneficial effects of such two-steps treatment at lab scale. In this paper, an innovative coupled solar-biological system at field pilot scale was designed, builds, and experimental results are presented. The strategy to develop this system implicates the choice of the most appropriate solar collector and the most efficient AOP, the optimization of this AOP, the choice of the biological oxidation system, the monitoring of the chemical and biological characteristics of photo-treated solutions and the evaluation of the performances of the coupled solar-biological flow system. The coupled system is conformed by a Compound Parabolic Solar Collector (CPC) and a Fixed Bed Reactor (FBR). The photo-Fenton system was the most appropriate AOP for the degradation of a model biorecalcitrant compound, 5-amino-6-methyl-2-benzimidazolone (AMBI). Surface Response Methodology was used to optimize the Fe3+ and H2O2 concentration. The coupled reactor, operates in semicontinuous mode, has shown to reach a whole mineralization performance between 80 and 90% in the range of initial dissolved organic carbon (DOC) concentration of 300–500 mg C l−1. These results indicate that coupling solar-biological processes at pilot scale is a plausible effective approach for the treatment of real industrial wastewaters.