In this work, a cylindrical flow-through electro-Fenton reactor integrated by graphite felt electrodes and Fe(II) loaded resin was evaluated for the production of the Fenton reaction mixture and for the degradation of amoxicillin (AMX) containing aqueous solutions. First, the influence of several factors such as treatment time, current intensity, flow rate and electrode position were investigated for the electrogeneration of H2O2 and the energetic consumption by means of a factorial design methodology using a 24 factorial matrix. Electric current and treatment time were found to be the pivotal parameters influencing the H2O2 production with respective contributions of 40.2% and 26.9%. The flow rate had low influence on the responses, however, 500 mL min-1 (with an average residence time of 1.09 min obtained in the residence time distribution analysis) allowed to obtain a better performance due to the high mass transport to and from the electrodes. As expected, polarization was also found to play an important role, since for cathode-to-anode flow direction, lower H2O2 concentrations were determined when compared with anode-to-cathode flow arrangement, indicating that part of the H2O2 produced in the cathode could be destroyed at the anode. A fluorescence study of hydroxyl radical production on the other hand, showed that higher yields were obtained using an anode-to-cathode flow direction (up to 3.88 µM), when compared with experiments carried out using a cathode-to-anode flow direction (3.11 µM). The removal of a commercial formulation of the antibiotic amoxicillin (AMX) was evaluated in terms of total organic carbon, achieving up to 57.9 % and 38.63% of the pollutant mineralization using synthetic and real sanitary wastewater spiked, respectively. Finally, the efficiency of the process on the inactivation of fecal coliforms in sanitary wastewater samples was assessed, reducing 90% of the bacterium after 5 min of electrolysis.