To understand the mechanisms causing running injuries, it is crucial to get insights into biomechanical loading in the runners' environment. Ground reaction forces (GRFs) describe the external forces on the body during running, however, measuring these forces is usually only possible in a gait laboratory. Previous studies show that it is possible to use inertial measurement units (IMUs) to estimate vertical forces, however, forces in anterior-posterior direction play an important role in the push-off. Furthermore, to perform an inverse dynamics approach, for modelling tissue specific loads, 3D GRFs are needed as input. Therefore, the goal of this work was to estimate 3D GRFs using three inertial measurement units. Twelve rear foot strike runners did nine trials at three different velocities (10, 12 and 14 km/h) and three stride frequencies (preferred and preferred ± 10%) on an instrumented treadmill. Then, data from IMUs placed on the pelvis and lower legs were used as input for artificial neural networks (ANNs) to estimate 3D GRFs. Additionally, estimated vertical GRF from a physical model was used as input to create a hybrid machine learning model. Using different splits in validation and training data, different ANNs were fitted and assembled into an ensemble model. Leave-one-subject-out cross-validation was used to validate the models. Performance of the machine learning, hybrid machine learning and a physical model were compared. The estimated vs. measured GRF for the hybrid model had a RMSE normalized over the full range of values of 10.8, 7.8 and 6.8% and a Pearson correlation coefficient of 0.58, 0.91, 0.97 for the mediolateral direction, posterior-anterior and vertical direction respectively. Performance for the three compared models was similar. The ensemble models showed higher model accuracy compared to the ensemble-members. This study is the first to estimate 3D GRF during continuous running from IMUs and shows that it is possible to estimate GRF in posterior-anterior and vertical direction, making it possible to estimate these forces in the outdoor setting. This step towards quantification of biomechanical load in the runners' environment is helpful to gain a better understanding of the development of running injuries.